Multi-layered, multiple unit pharmaceutical compositions

Abstract

The present invention relates to pharmaceutical compositions comprising multilayered multiple units and processes for the preparation thereof.

We claim: 
     
         1 . A multilayered multiple unit composition comprising:
 (i) an inert core;   (ii) a first layer on the inert core, the comprising:
 (a) at least one hydrophobic polymer or hydrophobic substance; and 
 (b) at least one pH-dependent polymer or pH-dependent substance; 
   (iii) a second layer onto the first layer, the second layer comprising at least one active ingredient;   (iv) a third layer onto the second layer, the third comprising one or more pharmaceutically acceptable polymers effective for controlling or modifying the release of the active ingredient; and   (v) optionally, a fourth layer onto the third layer, the fourth layer comprising one or more pharmaceutically acceptable polymers,   
       wherein the first layer is applied as a solution or dispersion in a non-aqueous based solvent system. 
     
     
         2 . The multilayered multiple unit composition according to  claim 1 , wherein the hydrophobic polymer or hydrophobic substance is present in the first layer in an amount of about 0.1% to 20% of the total weight of the composition. 
     
     
         3 . The multilayered multiple unit composition according to  claim 1 , wherein the pH-dependent polymer or pH-dependent substance is present in the first layer in an amount of about 0.1% to 20% of the total weight of the composition. 
     
     
         4 . The multilayered multiple unit composition according to  claim 1 , wherein the ratio of the hydrophobic polymer or hydrophobic substance to the pH-dependent polymer or pH-dependent substance in the first layer varies from about 99:1 to 1:99 by weight. 
     
     
         5 . The multilayered multiple unit composition according to  claim 1 , wherein a seal layer comprising one or more pharmaceutically acceptable polymers is optionally applied between the second active layer and the third controlled release or modified release layer. 
     
     
         6 . The multilayered multiple unit composition according to  claim 1 , wherein the composition is prepared using a process comprising the steps of:
 (i) providing an inert core;   (ii) applying a first layer on the inert core, the first layer comprising:
 (a) at least one hydrophobic polymer or hydrophobic substance; and 
 (b) at least pH-dependent polymer or pH-dependent substance; 
   (iii) applying a second layer onto the first layer, the second layer comprising at least one active ingredient;   (iv) applying a third layer onto the second layer, the third layer comprising one or more pharmaceutically acceptable polymers effective for controlling or modifying the release of the active ingredient; and   (v) optionally applying a fourth layer onto the third layer, the fourth layer comprising one or more pharmaceutically acceptable polymers,   
       wherein the first layer is applied as a solution, dispersion or suspension in a non-aqueous based solvent system. 
     
     
         7 . The multilayered multiple unit composition according to  claim 5 , wherein the composition is prepared using a process comprising the steps of:
 (i) providing an inert core;   (ii) applying a first layer on the inert core, the first layer comprising:
 (a) at least one hydrophobic polymer or hydrophobic substance; and 
 (b) at least one pH-dependent polymer or pH-dependent substance; 
   (iii) applying a second layer onto the first layer, the second layer comprising at least one active ingredient;   (iv) applying a seal layer onto the second layer, the seal layer comprising one or more pharmaceutically acceptable polymers;   (v) applying a third layer onto the seal layer, the third layer comprising one or more pharmaceutically acceptable polymers effective for controlling or modifying the release of the active ingredient; and   (vi) optionally applying a fourth layer onto the third layer, the fourth layer comprising one or more pharmaceutically acceptable polymers,   
       wherein the first layer is applied as a solution, dispersion or suspension in a non-aqueous based solvent system. 
     
     
         8 . The multilayered multiple unit composition according to  claim 5 , wherein the seal layer onto the second layer optionally includes one or more organic acids. 
     
     
         9 . The multilayered multiple unit composition according to  claim 1 , wherein the said composition includes one or more pharmaceutically acceptable excipients which act in one or more capacities as diluents, binders, plasticizers, lubricants, glidants, colorants, or flavoring agents. 
     
     
         10 . The multilayered multiple unit composition according to  claim 1 , wherein the composition is used to treat urinary disorders including overactive urinary bladder. 
     
     
         11 . The multilayered multiple unit composition according to  claim 1 , wherein the active ingredient comprises an antiulcer, analgesic, antihypertensive, antibiotic, antipsychotic, anticancer agent, antimuscarinic, diuretic, antimigraine, antiviral, anti-inflammatory agent, sedative, antidiabetic, antidepressant, antihistaminic, antiparasitic, antiepileptic, anti-Alzheimer's or lipid lowering drug 
     
     
         12 . The multilayered multiple unit composition according to  claim 1 , wherein the active ingredient comprises tolterodine.